Purpose: 1. To identify the receptors on malaria parasites for red cell invasion and on infected red cells for adhesion to endothelium and to placenta. 2. To identify the red cell receptors for each parasite ligand. 3.To identify the basis of the dichotomy between parasites that bind placenta and parasites that bind to endothelium. 4. Test a region on the variant antigen for inducing protection against P. falciparum in Aotus monkeys and for overcoming variation. Accomplishments during the year: 1. Identification of a new receptor on P. falciparum malaria parasites for binding to red cells and the receptor on the red cell to which it binds. 2. The domain on the variant antigen for binding chondroitin sulfate A in placenta has been identified. As the binding of infected red cells in placenta is associated with fetal and newborn mortality, blocking this with a vaccine may reduce disease. Antibodies to this domain appear to be cross- reactive to parasites from around the world. We are working on this domain as a vaccine candidate. We have identified the basis of the dichotomous binding to CD36 or CIDR1. 3. The first vaccine trial against one of the domain of the variant antigen (CIDR1) on the red cell surface for binding endothelium has been used in a vaccine in Aotus monkeys that protected against the homologous strain but not the heterologous one.